Drug Master File Submissions – An Overview

(This article summarizes a White Paper on DMF submissions prepared by EAS Independent Consultant Albert Yehaskel.)

Drug Master Files (DMFs) are detailed submissions to the Food and Drug Administration (FDA) that may be used to provide confidential details about facilities, processes, or articles used in the manufacturing, processing, packaging, and storing of one or more human drugs. Submitted solely at the discretion of the holder, the information contained in the DMF may be used to support drug applications, supplements to applications, export applications or other DMFs.

Prior to creating and submitting a DMF, FDA requires the drug firm to request a Pre-Assigned Application Number. Once the number is assigned, the DMF may be pDrug Master File Submissions – An Overviewrepared and submitted to FDA. The file must include five core modules providing quality and manufacturing details pertinent to chemistry, manufacturing and controls (CMC) and non-CMC related information (facilities, manufacturing, processing, packaging, and storage requirements) of the drug constituent. Additional items to be included are Letters of Authorization (LOAs) for who may reference the DMF, a user fee form demonstrating proper payments have been made for the submission of the DMF and administrative information, such as contacts within the filing firm and assignment of a U.S. agent. It is important that all required information is accurate and current for the DMF to be active. Also, the holder must provide an annual report on the anniversary date of the original submission to maintain the DMF’s active status. To be accepted for consideration in the New Drug Application (NDA) or Abbreviated New Drug Application (ANDA) in which it is referenced, the DMF must be current at the time of review.

DMFs are neither approved nor disapproved but are reviewed by FDA to determine whether the information contained is adequate to support a particular application which references it. Although the submission of a DMF is voluntary it can be a very important business tool, as it allows FDA to review claims of safety and quality of the constituent without revealing proprietary manufacturing information to another company using that constituent to manufacture a drug product. DMFs also accelerate FDA’s review process for Investigational New Drugs (INDs), NDAs, ANDAs and New Animal Drug Applications (NADAs). For this reason, the DMF must be continuously maintained and current at the time of FDA review and is an essential element in achieving a successful drug application, which can represent a multi-billion dollar profit potential for the drug product applicant.

Manufacturers with a large number of DMFs are often considered to be more reliable in terms of quality, regulatory standards, and capability to meet Current Good Manufacturer Practice (cGMP) requirements.

Effective May 5, 2017, FDA will require all DMFs to be submitted electronically through an Electronic Common Technical Document (eCTD) process submitted through FDA’s Center for Drug Evaluation and Research (CDER) Electronic Submissions Gateway (ESG). More details on the eCTD process can be found in the EAS white paper on DMF submissions as well as a previous EAS-E-News Issue of the Month article and background information on theEAS webpage. Should you or your company have questions on DMF submissions, LOAs or converting documents to the required eCTD process, please contact EAS to discuss your specific regulatory needs.